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Yorodumi- PDB-3qd4: Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 1,1... -
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-Basic information
Entry | Database: PDB / ID: 3qd4 | ||||||
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Title | Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 1,1-Dimethylethyl{(3R,5R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-5-methyl-3-piperidinyl}carbamate | ||||||
Components | 3-phosphoinositide-dependent protein kinase 1 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / kinase domain / AGC kinase / signal tranduction / ATP & Phosphoinositide / Phosphorylation on S241 / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information 3-phosphoinositide-dependent protein kinase activity / Activation of AKT2 / regulation of mast cell degranulation / negative regulation of toll-like receptor signaling pathway / type B pancreatic cell development / positive regulation of phospholipase activity / hyperosmotic response / RSK activation / regulation of canonical NF-kappaB signal transduction / positive regulation of vascular endothelial cell proliferation ...3-phosphoinositide-dependent protein kinase activity / Activation of AKT2 / regulation of mast cell degranulation / negative regulation of toll-like receptor signaling pathway / type B pancreatic cell development / positive regulation of phospholipase activity / hyperosmotic response / RSK activation / regulation of canonical NF-kappaB signal transduction / positive regulation of vascular endothelial cell proliferation / negative regulation of cardiac muscle cell apoptotic process / phospholipase activator activity / positive regulation of sprouting angiogenesis / Constitutive Signaling by AKT1 E17K in Cancer / CD28 dependent PI3K/Akt signaling / phospholipase binding / cellular response to epidermal growth factor stimulus / positive regulation of blood vessel endothelial cell migration / Role of LAT2/NTAL/LAB on calcium mobilization / Estrogen-stimulated signaling through PRKCZ / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / negative regulation of endothelial cell apoptotic process / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / extrinsic apoptotic signaling pathway / RHO GTPases activate PKNs / GPVI-mediated activation cascade / T cell costimulation / activation of protein kinase B activity / positive regulation of protein localization to plasma membrane / Integrin signaling / insulin-like growth factor receptor signaling pathway / positive regulation of release of sequestered calcium ion into cytosol / negative regulation of transforming growth factor beta receptor signaling pathway / VEGFR2 mediated vascular permeability / VEGFR2 mediated cell proliferation / epidermal growth factor receptor signaling pathway / cell projection / peptidyl-threonine phosphorylation / calcium-mediated signaling / negative regulation of protein kinase activity / cellular response to insulin stimulus / CLEC7A (Dectin-1) signaling / FCERI mediated NF-kB activation / Regulation of TP53 Degradation / G beta:gamma signalling through PI3Kgamma / positive regulation of angiogenesis / PIP3 activates AKT signaling / cell migration / Downstream TCR signaling / insulin receptor signaling pathway / actin cytoskeleton organization / cytoplasmic vesicle / protein autophosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / postsynaptic density / non-specific serine/threonine protein kinase / intracellular signal transduction / protein phosphorylation / protein serine kinase activity / focal adhesion / protein serine/threonine kinase activity / ATP binding / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Medina, J.R. / Becker, C.J. / Blackledge, C.W. / Duquenne, C. / Feng, Y. / Grant, S.W. / Heerding, D. / Li, W.H. / Miller, W.H. / Romeril, S.P. ...Medina, J.R. / Becker, C.J. / Blackledge, C.W. / Duquenne, C. / Feng, Y. / Grant, S.W. / Heerding, D. / Li, W.H. / Miller, W.H. / Romeril, S.P. / Scherzer, D. / Shu, A. / Bobko, M.A. / Chadderton, A.R. / Dumble, M. / Gradiner, C.M. / Gilbert, S. / Liu, Q. / Rabindran, S.K. / Sudakin, V. / Xiang, H. / Brady, P.G. / Campobasso, N. / Ward, P. / Axten, J.M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2011 Title: Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors. Authors: Medina, J.R. / Becker, C.J. / Blackledge, C.W. / Duquenne, C. / Feng, Y. / Grant, S.W. / Heerding, D. / Li, W.H. / Miller, W.H. / Romeril, S.P. / Scherzer, D. / Shu, A. / Bobko, M.A. / ...Authors: Medina, J.R. / Becker, C.J. / Blackledge, C.W. / Duquenne, C. / Feng, Y. / Grant, S.W. / Heerding, D. / Li, W.H. / Miller, W.H. / Romeril, S.P. / Scherzer, D. / Shu, A. / Bobko, M.A. / Chadderton, A.R. / Dumble, M. / Gardiner, C.M. / Gilbert, S. / Liu, Q. / Rabindran, S.K. / Sudakin, V. / Xiang, H. / Brady, P.G. / Campobasso, N. / Ward, P. / Axten, J.M. #1: Journal: ACS Med. Chem. Lett. / Year: 2010 Title: Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery Authors: Medina, J.R. / Blackledge, C.W. / Heerding, D.A. / Campobasso, N. / Ward, P. / Briand, J. / Wright, L. / Axten, J.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3qd4.cif.gz | 71.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3qd4.ent.gz | 52.1 KB | Display | PDB format |
PDBx/mmJSON format | 3qd4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qd/3qd4 ftp://data.pdbj.org/pub/pdb/validation_reports/qd/3qd4 | HTTPS FTP |
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-Related structure data
Related structure data | 3qcqC 3qcsC 3qcxC 3qcyC 3qd0C 3qd3C C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 35652.852 Da / Num. of mol.: 1 / Fragment: kinase domain, residues 48-359 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDK1, PDPK1 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O15530, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-3Q6 / |
#3: Chemical | ChemComp-SO4 / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.94 Å3/Da / Density % sol: 58.19 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 9 Details: 1.9-2 M ammonium sulfate,0.1 M tris pH 9. and 5mM ATP; 15-30% glycerol plus mother liquor mixed with inhibitor served as the cryo-protectant before being frozen in liquid nitrogen, Vapor ...Details: 1.9-2 M ammonium sulfate,0.1 M tris pH 9. and 5mM ATP; 15-30% glycerol plus mother liquor mixed with inhibitor served as the cryo-protectant before being frozen in liquid nitrogen, Vapor diffusion. sitting drop, temperature 293K |
-Data collection
Diffraction | Mean temperature: 110 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.97872 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Oct 12, 2009 / Details: diamond | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: diamond / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97872 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.3→30 Å / Num. obs: 18792 / % possible obs: 99.9 % / Redundancy: 7.1 % / Rmerge(I) obs: 0.078 / Χ2: 1.01 / Net I/σ(I): 9.3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→29.859 Å / Occupancy max: 1 / Occupancy min: 0.16 / SU ML: 0.28 / σ(F): 0.05 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 33.34 Å2 / ksol: 0.352 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 95.01 Å2 / Biso mean: 39.7667 Å2 / Biso min: 23.26 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→29.859 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 13
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